Gamma glutamyl transpeptidase in safrole-induced, presumptive premalignant mouse hepatocytes

A histochemical procedure was used to determine the presenceof -glutamyl transpeptidase (GGT) in the livers of control,regenerating and carcinogen-treated mice. Young Balb/c micewere fed safrole, a naturally occurring hepatocarcinogen (0.4%w/w), for one year. Ten mice from control and ten mice fromthe safrole-treated group were killed at 4,8,16,24,36, and 52weeks of exposure and 9 adult mice were killed after 2/3 hepatectomy.Basophilic and acidophilic foci of altered hepatocytes occurredin safrole-treated mice after 24 weeks. Neoplastic nodules appearedafter 36 weeks. Both foci and nodules displayed elevated GGTactivity as determined by enzyme histochemistry. Variabilityin the pattern of enzyme distribution and staining intensitywas seen between cells of the same focus or nodule, as wellas between different foci and nodules. Hepatocytes from regeneratinglivers of partially hepatectomized mice were negative for GGT.These results demonstrated a sequential development of carcinogen-alteredhepatocyte populations characterized by the appearance of GGTactivity prior to carcinoma formation. The results in the mouseshow marked similarity to those reported in rat liver, whereGGT has been used as a positive marker for premalignant liverlesions induced by a variety of carcinogens.